CN114315497A - Method for synthesizing beta-myrcene through intermolecular nucleophilic addition reaction - Google Patents
Method for synthesizing beta-myrcene through intermolecular nucleophilic addition reaction Download PDFInfo
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- UAHWPYUMFXYFJY-UHFFFAOYSA-N beta-myrcene Chemical compound CC(C)=CCCC(=C)C=C UAHWPYUMFXYFJY-UHFFFAOYSA-N 0.000 title claims abstract description 308
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000005935 nucleophilic addition reaction Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 230
- 150000003839 salts Chemical class 0.000 claims abstract description 76
- 229910052751 metal Inorganic materials 0.000 claims abstract description 75
- 239000002184 metal Substances 0.000 claims abstract description 75
- 239000003446 ligand Substances 0.000 claims abstract description 72
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- 239000003054 catalyst Substances 0.000 claims abstract description 67
- WFYPICNXBKQZGB-UHFFFAOYSA-N butenyne Chemical group C=CC#C WFYPICNXBKQZGB-UHFFFAOYSA-N 0.000 claims abstract description 65
- 239000002994 raw material Substances 0.000 claims abstract description 12
- 239000000654 additive Substances 0.000 claims abstract description 8
- 230000000996 additive effect Effects 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 93
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 90
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052737 gold Inorganic materials 0.000 claims description 2
- 229910052741 iridium Inorganic materials 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 58
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
- 239000007789 gas Substances 0.000 description 35
- 238000010438 heat treatment Methods 0.000 description 30
- 238000010813 internal standard method Methods 0.000 description 30
- 238000001816 cooling Methods 0.000 description 29
- 238000006555 catalytic reaction Methods 0.000 description 25
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 22
- WTARULDDTDQWMU-RKDXNWHRSA-N (+)-β-pinene Chemical compound C1[C@H]2C(C)(C)[C@@H]1CCC2=C WTARULDDTDQWMU-RKDXNWHRSA-N 0.000 description 17
- WTARULDDTDQWMU-IUCAKERBSA-N (-)-Nopinene Natural products C1[C@@H]2C(C)(C)[C@H]1CCC2=C WTARULDDTDQWMU-IUCAKERBSA-N 0.000 description 17
- WTARULDDTDQWMU-UHFFFAOYSA-N Pseudopinene Natural products C1C2C(C)(C)C1CCC2=C WTARULDDTDQWMU-UHFFFAOYSA-N 0.000 description 17
- XCPQUQHBVVXMRQ-UHFFFAOYSA-N alpha-Fenchene Natural products C1CC2C(=C)CC1C2(C)C XCPQUQHBVVXMRQ-UHFFFAOYSA-N 0.000 description 17
- 229930006722 beta-pinene Natural products 0.000 description 17
- LCWMKIHBLJLORW-UHFFFAOYSA-N gamma-carene Natural products C1CC(=C)CC2C(C)(C)C21 LCWMKIHBLJLORW-UHFFFAOYSA-N 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 8
- HNVRRHSXBLFLIG-UHFFFAOYSA-N 3-hydroxy-3-methylbut-1-ene Chemical compound CC(C)(O)C=C HNVRRHSXBLFLIG-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 238000005336 cracking Methods 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- UHOVQNZJYSORNB-MZWXYZOWSA-N deuterated benzene Substances [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 5
- 238000005265 energy consumption Methods 0.000 description 5
- 238000006116 polymerization reaction Methods 0.000 description 5
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- BZAZNULYLRVMSW-UHFFFAOYSA-N 2-Methyl-2-buten-3-ol Natural products CC(C)=C(C)O BZAZNULYLRVMSW-UHFFFAOYSA-N 0.000 description 3
- 241000779819 Syncarpia glomulifera Species 0.000 description 3
- VYBREYKSZAROCT-UHFFFAOYSA-N alpha-myrcene Natural products CC(=C)CCCC(=C)C=C VYBREYKSZAROCT-UHFFFAOYSA-N 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000002304 perfume Substances 0.000 description 3
- 239000001739 pinus spp. Substances 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229940036248 turpentine Drugs 0.000 description 3
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 2
- HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 description 2
- 239000005792 Geraniol Substances 0.000 description 2
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 description 2
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 description 2
- 229910019032 PtCl2 Inorganic materials 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 238000000889 atomisation Methods 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002309 gasification Methods 0.000 description 2
- 229940113087 geraniol Drugs 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000012434 nucleophilic reagent Substances 0.000 description 2
- 238000000197 pyrolysis Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000004227 thermal cracking Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LAXRNWSASWOFOT-UHFFFAOYSA-J (cymene)ruthenium dichloride dimer Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ru+2].[Ru+2].CC(C)C1=CC=C(C)C=C1.CC(C)C1=CC=C(C)C=C1 LAXRNWSASWOFOT-UHFFFAOYSA-J 0.000 description 1
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000021559 Dicerandra Species 0.000 description 1
- 235000010654 Melissa officinalis Nutrition 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000005498 polishing Methods 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention provides a method for synthesizing beta-myrcene by intermolecular nucleophilic addition reaction. The method uses compound I
And vinyl acetylene
Description
Technical Field
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a method for synthesizing beta-myrcene by intermolecular nucleophilic addition.
Background
Beta-myrcene, also known as myrcene, has pleasant sweet and balm odor, can be directly used as a perfume, is one of the most important raw materials and intermediates in the perfume industry, and can also be used for synthesizing other perfumes. The source of the beta-myrcene mainly comprises natural extraction and artificial synthesis. Currently, the artificial synthesis is the main source of beta-myrcene and is mainly synthesized by pyrolysis of beta-pinene.
Patent CN107602322A reports a process and a production device for producing beta-myrcene by thermal cracking of beta-pinene, and the authors reduce the temperature of atomization and gasification of beta-pinene by processing raw material beta-pinene into micron-sized droplets through ultrasonic atomization. The cracking temperature is still particularly high, namely 400-700 ℃, and the purity of the obtained beta-myrcene with mass yield is only 79.6% at best.
The purity of the crude product obtained by beta-pinene cracking reaction is usually only 70-80%, continuous purification is required, and a polymerization inhibitor is required to be added during purification to prevent product polymerization. Patent CN108658719A reports a purification method of beta-myrcene obtained by thermal cracking of beta-pinene. The authors purified beta-myrcene by dehydrogenation and heavy two-step rectification with the addition of a polymerization inhibitor.
In a word, the route for synthesizing the beta-myrcene by the beta-pinene generally has the characteristics of high temperature, high energy consumption, high device requirement and the like, and in addition, the beta-myrcene has more unsaturated double bonds, has active chemical properties and is extremely unstable under the high-temperature cracking condition, so the product purity of general cracking reaction is lower, and a polymerization inhibitor is generally required to be added during purification.
In addition, beta-pinene exists in turpentine, so that the turpentine resources in China are rich, but the price of the turpentine fluctuates greatly with the increase of the labor cost, and the price is greatly increased in recent years, so that the cost of the downstream beta-myrcene is increased.
In addition, isoprene routes have also been reported. The method has the advantages of wide raw material source, reaction route segment and simple process operation, but cannot realize industrial production due to the problems of poor selectivity, low yield and the like of the beta-myrcene.
In addition, the synthesis of beta-myrcene by a geranium-pure route has also been reported. CN111454114A reports synthesis of lauryl alcohol by geraniol, which does not use metal catalyst and additive, and has mild reaction, but uses geraniol with higher economic value to synthesize beta-myrcene, which has no commercial value in industry.
In summary, with the rapid development of the fragrance industry and the cosmetic industry, the demand for β -myrcene has increased year by year. At present, the synthetic route of the beta-myrcene has a plurality of defects, so that the development of a new route with low energy consumption, high selectivity and mild conditions for synthesizing the beta-myrcene has important significance.
Disclosure of Invention
The invention provides a method for synthesizing beta-myrcene by intermolecular nucleophilic addition reaction, which has the advantages of cheap and easily-obtained raw materials, low reaction temperature, simple operation, high selectivity and high yield.
In order to achieve the above objects and achieve the above technical effects, the invention adopts the following technical scheme:
a method for synthesizing beta-myrcene through intermolecular nucleophilic addition reaction takes a compound of a formula I and vinyl acetylene as initial raw materials, an alkali additive is added, and the beta-myrcene is obtained through the intermolecular nucleophilic addition reaction under the action of a catalyst formed by metal salt and a ligand;
wherein R is1One of H, C1-C10 alkyl, C3-C8 unsubstituted cycloalkyl, C3-C8 substituted cycloalkyl, phenyl, substituted phenyl, benzyl and substituted benzyl, wherein the substituent is selected from one or more of C1-C10 alkyl, C1-C10 alkoxy, halogen and nitro; preferably R1Is one of C1-C10 alkyl; more preferably R1is-CH3、-CH2CH3、-CH2One of Ph.
In one embodiment, the substrate I generates a nucleophilic reagent under the action of alkali, the vinyl acetylene generates a nucleophilic reagent under the action of a catalyst, an alkyne bond in the vinyl acetylene is activated to serve as an electrophilic reagent, and then the substrate I and the electrophilic reagent are subjected to substitution reaction to obtain the beta-myrcene. Illustratively, the reaction formula of the above method is:
in the present invention, the molar ratio of the compound of formula I to vinylacetylene is 1:0.5-2, preferably 1: 1.2-1.3.
In the invention, the reaction conditions are that the reaction is firstly carried out for 0.5-24h at 0-70 ℃, then carried out for 0.5-24h at 80-160 ℃, preferably firstly carried out for 12h at 40-60 ℃ and then carried out for 6h at 100-120 ℃.
In the invention, the alkali additive is triethylamine, potassium tert-butoxide, KOH, NaOH or K2CO3、Na2CO3、NaHCO3One or more of (a), preferably triethylamine; preferably, the molar ratio of the base additive to the compound of formula I is from 0.1 to 5:1, preferably from 2 to 3: 1.
In the present invention, the catalyst formed by the metal salt and the ligand is a complex formed by the metal salt and the ligand of formula II:
wherein R is2-R11Is one or more of alkyl of H, C1-C10, unsubstituted cycloalkyl of C3-C8, substituted cycloalkyl of C3-C8, phenyl, substituted phenyl, benzyl and substituted benzyl; the substituent is selected from one or more of C1-C10 alkyl, C1-C10 alkoxy, halogen and nitro; preferably R2-R11Is one or more of alkyl, phenyl and substituted phenyl of H, C1-C10; more preferably R2Is composed oftBu、R3-R11Is H, i.e., a ligand of formula II-1.
In the present invention, the metal salt is selected from one or more of salts containing Ru, Rh, Pt, Pd, Ir, Ni, Cu, Zn, Fe, and Au, preferably a metal salt containing Au; more preferably a metal saltIs AuNTf2、AuOTf2、AuSbF6One or more of (a).
In the present invention, the molar ratio of the metal salt to the ligand is (0.5-1.1):1, preferably (0.9-1): 1.
In the present invention, the molar ratio of the catalyst comprising the metal salt and the ligand to the compound I is (0.001-0.1):1, preferably (0.01-0.05): 1.
In the present invention, the reaction is carried out in a medium; preferably, the medium is one or more of methanol, ethanol, benzene, toluene, xylene, ethyl acetate, dichloromethane, dichloroethane, tetrahydrofuran, diethyl ether, preferably dichloromethane.
It is another object of the present invention to provide a beta-myrcene product.
The beta-myrcene product is prepared by adopting the method for synthesizing the beta-myrcene through intermolecular nucleophilic addition reaction.
In the present invention, unless otherwise specified, all the pressures are absolute pressures.
Compared with the prior art, the technical scheme of the invention has the advantages that:
1) at present, the beta-myrcene synthesized by the beta-pinene cracking reaction has low reaction selectivity, so that the product is complicated to purify, and a polymerization inhibitor is often additionally added to prevent the product from polymerizing. By the novel synthetic route, the beta-myrcene can be synthesized with high conversion rate (up to 95% under the preferred condition) and high selectivity (up to 96% under the preferred condition), and the further purification of the product is very simple.
2) At present, the industrially synthesized beta-myrcene is obtained by pyrolysis of beta-pinene, not only has high energy consumption, but also has high requirements on equipment, and the route of the invention has low reaction temperature (50-120 ℃), relatively mild conditions and simple device.
3) In addition, the raw materials used in the new route are very easy to synthesize from bulk raw materials, are low in price, are less influenced by various factors compared with the natural sources of the raw materials of the traditional route at present, and have stronger competitiveness.
Detailed description of the invention
The process of the present invention is further illustrated by the following specific examples, but the invention is not limited to the examples listed, but also encompasses any other known modifications within the scope of the claims of the invention.
An analytical instrument:
1) type of nuclear magnetic resonance spectrometer: BRUKER ADVANCEⅢ400，400MHz,C6D6Or CDCl3As a solvent;
2) gas chromatograph: agilent7890, a DB-5 separation column, a gasification chamber at 300 ℃, a detector at 300 ℃, a temperature raising program, an initial temperature of 40 ℃, a constant temperature of 10min, a temperature raising to 190 ℃ at 3 ℃/min, a temperature raising to 300 ℃ at 20 ℃/min, and a constant temperature of 6 min.
Information of main raw materials:
trimethyl orthoacetate, triethyl orthoacetate, 2-methyl-3-buten-2-ol, beta-pinene, chemical purity 98%, alatin reagent ltd;
propionic acid with chemical purity of more than or equal to 99%, Aladdin reagent Co., Ltd;
vinyl acetylene, chemical purity not less than 99.5%, Wuhan Yishi Tuopau science and technology Limited;
[RuCl2(p-cymene)]2、[Cp*RhCl2]2、PtCl2、Pd(OAc)2、NiCl2、AuNTf2、AuOTf2、AuSbF6chemical purity of>99%, carbofuran reagents ltd;
ligands II-1, II-2, II-3, II-4, chemical purity > 99%, carbofuran reagents GmbH;
triethylamine, potassium tert-butoxide, sodium hydroxide and sodium bicarbonate with a chemical purity of not less than 99%, Aladdin reagent Co., Ltd;
dichloromethane, dichloroethane, toluene, tetrahydrofuran, chemical purity > 99.5%, alatin reagent limited;
the main synthesis equipment comprises: three-mouth glass flask, four-mouth glass bottle with jacket, heating and refrigerating constant temperature circulator, constant temperature oil bath, Schlenk round bottom flask and pressure resistant kettle.
Example i
Compound I-1 was synthesized.
Trimethyl orthoacetate (1mol), 2-methyl-3-buten-2-ol (1mol) and propionic acid (0.2mol) are added into a flask, then the reaction system is heated to 125 ℃, the stirring reaction is continued for 12 hours, and the reaction is stopped. Sequentially using water and saturated NaHCO3And brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure at 70 ℃ under 30hPa to obtain Compound I (yield 98%). The characterization result is as follows:1H NMR(400MHz,CDCl3):δ1.61(s,3H),1.67(s,3H),2.30–2.35(m,4H),3.68(s,3H),5.08–5.10(m,1H)；13CNMR(100MHz,CDCl3):δ17.7,23.4,25.5,34.1,51.4,122.3,133.1,173.5。
example ii
Compound I-2 was synthesized.
Triethyl orthoacetate (1mol), 2-methyl-3-buten-2-ol (1mol) and propionic acid (0.2mol) were added to a flask, and then the reaction system was heated to 125 ℃ and stirred to continue the reaction for 12 hours, and the reaction was stopped. Sequentially using water and saturated NaHCO3And brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure at 70 ℃ under 20hPa to obtain Compound I (yield 98%). The characterization result is as follows:1H NMR(400MHz,CDCl3):δ1.26(t,3H),1.61(d,3H),1.67(d,3H),2.27–2.33(m,4H),4.12(q,2H),5.04-5.14(m,1H)；13C NMR(100MHz,CDCl3):14.1,17.4,23.6,25.5,34.3,60.1,122.4,132.7,173.1。
example 1
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2Is used as a catalyst to catalyze after being complexed with ligand II-1Reacting to prepare beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 96 percent and the selectivity of the beta-myrcene is 96 percent. The characterization result is as follows:1H NMR(400MHz,C6D6):δ1.52(s,3H),1.65–1.66(m,3H),2.19-2.26(m,4H),4.95(d,1H),4.97–4.98(m,2H),5.16–5.21(m,1H),5.20(d,1H)，6.35(dd,1H)；13C NMR(100MHz,C6D6):δ17.6,25.7,27.1,31.8,113.0,116.1,124.6,131.5,139.4,146.3。
example 2
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound II-2(1mol, 1equiv) in example i were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 94% and the selectivity of beta-myrcene is 94%.
Example 3
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. The catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-3 of example I were then mixed
(1mol, 1equiv) was charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 92% and the selectivity of the beta-myrcene is 91%.
Example 4
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (0.5mol, 0.5equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 82% and the selectivity of the beta-myrcene is 82%.
Example 5
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (2mol, 2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 97 percent and the selectivity of the beta-myrcene is 90 percent.
Example 6
Synthesizing the compound beta-myrcene.
Metal salt [ RuCl ]2(p-cymene)]2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Under the protection of nitrogen, a metal salt [ RuCl ] is added into a three-neck flask2(p-cymene)]2(0.015mol, 1.5 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 82% and the selectivity of the beta-myrcene is 81%.
Example 7
Synthesizing the compound beta-myrcene.
Metal salt [ Cp RhCl2]2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Under the protection of nitrogen, a metal salt [ Cp & RhCl ] is added into a three-neck flask2]2(0.015mol, 1.5 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 80% and the selectivity of the beta-myrcene is 80%.
Example 8
Synthesizing the compound beta-myrcene.
Metal salt PtCl2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt PtCl into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 78% and the selectivity of the beta-myrcene is 83%.
Example 9
Synthesizing the compound beta-myrcene.
Metal salt Pd (OAc)2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Under the protection of nitrogen, a metal salt Pd (OAc) is added into a three-neck flask2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 82% and the selectivity of the beta-myrcene is 82%.
Example 10
Synthesizing the compound beta-myrcene.
Metallic salt NiCl2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Under the protection of nitrogen, adding metal salt NiCl into a three-neck flask2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 81 percent and the selectivity of the beta-myrcene is 84 percent.
Example 11
Synthesizing the compound beta-myrcene.
Metal salt AuOTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Under the protection of nitrogen, adding metal salt AuOTf into a three-neck flask2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of bisMethyl chloride, stirring at room temperature for 1 h. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 91% and the selectivity of the beta-myrcene is 92%.
Example 12
Synthesizing the compound beta-myrcene.
Metal salt AuSbF6And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Under the protection of nitrogen, metal salt AuSbF is added into a three-neck flask6(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 92% and the selectivity of the beta-myrcene is 96%.
Example 13
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And ligand II-2
The complex is used as a catalyst to catalyze the reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-2(0.033mol, 3.3 mol%), 200 ml of dichloromethane was added,stir at room temperature for 1 h. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 92% and the selectivity of the beta-myrcene is 95%.
Example 14
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And ligand II-3
The complex is used as a catalyst to catalyze the reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-3(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 90% and the selectivity of beta-myrcene is 94%.
Example 15
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And ligand II-4
The complex is used as a catalyst to catalyze the reaction to prepare the beta-myrcene.
Under the protection of nitrogen, in a three-neck flaskAdding metal salt AuNTf2(0.03mol, 3 mol%) and ligand II-4(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 91% and the selectivity of the beta-myrcene is 93%.
Example 16
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.06mol, 6 mol%), 200 ml dichloromethane was added and stirred at room temperature for 1 h. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 87% and the selectivity of the beta-myrcene is 91%.
Example 17
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.027mol, 2.7 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 h. Then is going up toThe catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 92% and the selectivity of the beta-myrcene is 95%.
Example 18
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.001mol, 0.1 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 83 percent and the selectivity of the beta-myrcene is 83 percent.
Example 19
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.1mol, 10 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, and a vinyl group was introducedAcetylene (1.2mol, 1.2equiv) was added, and the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 97 percent and the selectivity of the beta-myrcene is 98 percent.
Example 20
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, potassium tert-butoxide (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 84% and the selectivity of the beta-myrcene is 82%.
Example 21
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, NaOH (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping reaction, cooling to room temperature, and discharging residual vinyl acetylene in the systemAnd then heating to 115 ℃ for continuous reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction liquid by a gas phase internal standard method, wherein the conversion rate is 85 percent, and the selectivity of the beta-myrcene is 86 percent.
Example 22
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then the catalyst solution and NaHCO are added3(2.5mol, 2.5equiv) and the compound I (1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 86% and the selectivity of the beta-myrcene is 83%.
Example 23
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (0.1mol, 0.1equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 80 percent, and the reaction solution is beta-monthlyThe selectivity of myrcene is 96 percent.
Example 24
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (5mol, 5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 94% and the selectivity of beta-myrcene is 96%.
Example 25
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of toluene was added, and the mixture was stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 84% and the selectivity of the beta-myrcene is 86%.
Example 26
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml tetrahydrofuran was added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 86% and the selectivity of the beta-myrcene is 88%.
Example 27
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloroethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 50 ℃ to react for 12 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 115 ℃ to continue the reaction for 6 hours, stopping the reaction, opening the reaction kettle, and analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 88% and the selectivity of the beta-myrcene is 91%.
Example 28
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2The complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene。
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 0 ℃ to react for 24 hours. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 80 ℃, continuing the reaction for 24 hours, stopping the reaction, opening the reaction kettle, analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 87%, and the selectivity of the beta-myrcene is 93%.
Example 29
Synthesizing the compound beta-myrcene.
Metal salt AuNTf2And the complex of the beta-myrcene and a ligand II-1 is used as a catalyst for catalytic reaction to prepare the beta-myrcene.
Adding metal salt AuNTf into a three-neck flask under the protection of nitrogen2(0.03mol, 3 mol%) and ligand II-1(0.033mol, 3.3 mol%), 200 ml of dichloromethane were added and stirred at room temperature for 1 hour. Then, the above catalyst solution, triethylamine (2.5mol, 2.5equiv) and the compound I-1(1mol, 1equiv) in example I were charged into a pressure-resistant reaction vessel, vinylacetylene (1.2mol, 1.2equiv) was introduced, and then the above system was heated to 70 ℃ for reaction for 0.5 h. Stopping the reaction, cooling to room temperature, removing the residual vinyl acetylene in the system, heating to 160 ℃, continuing the reaction for 0.5h, stopping the reaction, opening the reaction kettle, analyzing the reaction solution by a gas phase internal standard method, wherein the conversion rate is 92% and the selectivity of the beta-myrcene is 84%.
Comparative example 1
Synthesizing the compound beta-myrcene.
Beta-myrcene is prepared by the scheme of example 8 in patent CN 101045672.
Beta-pinene is used as a raw material, the beta-pinene is preheated to 300 ℃, then the beta-pinene is mixed with nitrogen at the temperature of 600 ℃ through a gas mixer, the mass ratio of the beta-pinene to the nitrogen is 1:3, the temperature of the mixed gas is 520 ℃, then the gas passes through an internal polishing type tubular reactor with the diameter of 25m and the length of 2m, nitrogen at the temperature of 520 ℃ is introduced again at the position 0.5m away from an inlet, the mass ratio of the beta-pinene to the nitrogen is 1:6, and the wall temperature is controlled at 500 ℃. After the gas leaves the reactor, the gas is condensed by a heat exchanger to obtain a product beta-myrcene, and the content of myrcene is 83 percent by analysis of a gas chromatography internal standard method.
Through comparison between the comparative example 1 and the example 1, the present industrial synthesis of beta-myrcene through beta-pinene cracking has the characteristics of high temperature (500 ℃.), high energy consumption, high device requirement and the like, and the selectivity is only 83%, while the route reported by the invention has the advantages of low reaction temperature (50-115 ℃), mild conditions, very low energy consumption, simple device, 96% of selectivity, and very simple further purification of the product.
It will be appreciated by those skilled in the art that modifications or adaptations to the invention may be made in light of the teachings of the present specification. Such modifications or adaptations are intended to be within the scope of the present invention as defined in the claims.
Claims (8)
1. A method for synthesizing beta-myrcene through intermolecular nucleophilic addition reaction is characterized in that a compound of a formula I and vinyl acetylene are used as initial raw materials, an alkali additive is added, and the beta-myrcene is obtained through intermolecular nucleophilic addition reaction under the action of a catalyst formed by a metal salt and a ligand;
wherein R is1One of H, C1-C10 alkyl, C3-C8 unsubstituted cycloalkyl, C3-C8 substituted cycloalkyl, phenyl, substituted phenyl, benzyl and substituted benzyl, wherein the substituent is selected from one or more of C1-C10 alkyl, C1-C10 alkoxy, halogen and nitro; preferably R1Is one of C1-C10 alkyl; more preferably R1is-CH3、-CH2CH3、-CH2One of Ph.
2. The process according to claim 1, wherein the molar ratio of the compound of formula I to vinylacetylene is 1:0.5-2, preferably 1: 1.2-1.3.
3. The process according to claim 1 or 2, wherein the reaction conditions are first 0-70 ℃ for 0.5-24h, then 80-160 ℃ for 0.5-24h, preferably first 40-60 ℃ for 12h, and then 100-120 ℃ for 6 h.
4. The method according to any one of claims 1-3, wherein the base additive is triethylamine, potassium tert-butoxide, KOH, NaOH, K2CO3、Na2CO3、NaHCO3One or more of (a), preferably triethylamine;
preferably, the molar ratio of the base additive to the compound of formula I is from 0.1 to 5:1, preferably from 2 to 3: 1.
5. The method of any one of claims 1 to 4, wherein the catalyst formed by the metal salt and the ligand is a complex of the metal salt and a ligand of formula II:
wherein R is2-R11Is one or more of alkyl of H, C1-C10, unsubstituted cycloalkyl of C3-C8, substituted cycloalkyl of C3-C8, phenyl, substituted phenyl, benzyl and substituted benzyl; the substituent is selected from one or more of C1-C10 alkyl, C1-C10 alkoxy, halogen and nitro; preferably R2-R11Is one or more of alkyl, phenyl and substituted phenyl of H, C1-C10; more preferably R2Is composed oftBu、R3-R11Is H, a ligand of formula II-1;
and/or the metal salt is selected from Ru, Rh,One or more of salts of Pt, Pd, Ir, Ni, Cu, Zn, Fe and Au, preferably a metal salt containing Au; more preferably, the metal salt is AuNTf2、AuOTf2、AuSbF6One or more of (a).
6. The process according to claim 1, wherein the molar ratio of metal salt to ligand is (0.5-1.1) to 1, preferably (0.9-1) to 1;
and/or the molar ratio of the catalyst consisting of the metal salt and the ligand to the compound I is (0.001-0.1):1, preferably (0.01-0.05): 1.
7. The process according to any one of claims 1 to 6, characterized in that the reaction is carried out in a medium;
preferably, the medium is one or more of methanol, ethanol, benzene, toluene, xylene, ethyl acetate, dichloromethane, dichloroethane, tetrahydrofuran, diethyl ether, preferably dichloromethane.
8. A β -myrcene product obtained by the method of synthesizing β -myrcene by intermolecular nucleophilic addition reaction according to any one of claims 1 to 7.
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| US4003958A (en) * | 1974-09-26 | 1977-01-18 | Nissan Chemical Industries, Ltd. | Process for producing myrcene |
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